Inflammation induces bitter taste oversensitization via epigenetic changes inTas2rgene clusters

Abstract

SummaryT2R bitter receptors, encoded byTas2rgenes, are not only critical for bitter taste signal transduction but also important for defense against bacteria and parasites. However, little is known about whether and howTas2rgene expression are regulated. Here we show that, in an inflammation model mimicking bacterial infection, the expression of manyTas2rsare significantly up-regulated and mice displayed markedly increased neural and behavioral responses to bitter compounds. Using single-cell assays for transposase-accessible chromatin with sequencing (scATAC-seq), we found that the chromatin accessibility ofTas2rswas highly cell type specific and inflammation increased the accessibility of manyTas2rs. scATAC-seq also revealed substantial chromatin remodeling in immune response genes in taste tissue stem cells, suggesting potential long-term effects. Together, our results suggest an epigenetic mechanism connecting inflammation,Tas2rgene regulation, and altered bitter taste, which may explain heightened bitter taste that can occur with infections and cancer treatments.